Objective To explore the expression of a new candidate tumor suppressor N-myc downstream regulated gene 2 (NDRG2) in bladder cancer tissues and to investigate its clinical and pathological significance.Methods Formalin-fixed,paraffin-embedded tissue sections from 62 cases of bladder carcinomas and 10 cases of normal bladder tissues were analyzed retrospectively with immunohistochemistry (S-P method).Results The NDRG2 gene was highly expressed in normal bladder tissues,but low expressed in bladder carcinoma tissues.Positive expression of NDRG2 was detected in 8 of the 10 (80.0％) normal tissues and 40.3％ in bladder carcinoma ones (x2 =3.98,P ＜0.05).Furthermore,with the degree of malignancy increased,the positive expression of NDRG2 in bladder carcinoma samples was decreased.The expression of NDRG2 in bladder carcinoma was negatively correlated(r =-0.288,P ＜0.05) with C-myc(r =-0.436,P ＜0.01) and positively correlated with p53 in bladder carcinoma tissues(r =0.717,P ＜0.01).Conclusions The level of NDRG2 expression was lower in bladder carcinomas than in normal tissues.NDRG2 may play an important role in bladder carcinogenesis and in the progress of bladder cancers.

Objective To investigate the antitumor activities of adenovirus-mediated NDRG2 gene (Ad-NDRG2) and docetaxel on human prostate cancer DU145 cells.Methods The protein expressions of cyclin D1,cycliu E,and NDRG2 in the cells were determined by Western blot.MTT and flow cytometry were used to observe the effects of docetaxel (10-6 mol/L,10-7 mol/L,and 10-s mol/L) and Ad-NDRG2 on prostate cancer cell line DU145 in single or synergistic administration ways for 24 and 48 hours in vitro.Male BALB/C-nu mice with DU145 prostate cancer cell lines were treated by docetaxel and Ad-NDRG2 singly or synergistically in vivo.Results After infected by adenovirus,the protein expression of NDRG2 increased,but cyclin D1 and cyclin E decreased in DU145 cells.Ad-NDRG2 inhibited the cell growth (inhibition ratio =41.8％,t =4.18,P ＜0.01),promoted apoptosis (apoptosis ratio =32.4％,x2 =11.66,P ＜0.05),changed the ratio of G2/M phase from 50.2％ to 23.6％,and reversed partially the G2/M arrest,of DU145 cells induced by 10-7 mol/L docetaxel.In vivo experiment showed that docetaxel,Ad-NDRG2,and combination of docetaxel and Ad-NDRG2 inhibited tumor growth with a inhibition rate of 30.7％,28.2％,and 55.8％,respectively.The coefficient of drug interaction (CDI) of docetaxel and Ad-NDRG2 was 0.89.Conclusions Ad-NDRG2 can enhance the growth suppression and apoptosis induced by docetaxel in synergistic way in vitro and in vivo.It demonstrated the great potential of Ad-NDRG2 in the treatment of androgen-independent prostate carcinoma.

Objective To explore the relation between vitamin D deficiency and susceptibility to spinal tuberculosis. Methods A total of 163 hospitalized patients with untreated spinal tuberculosis in Tianjin Haihe hospital were enrolled in this study from June 2013 to May 2016. A total of 170 individuals participated in health examination program at the same period were enrolled as the control group. The serum level of 25-hydroxyvitamin D [25(OH)D] was measured by enzyme linked immunosorbent assay. The 25(OH)D grading included serious deficiency group (<25 nmol/L), deficiency group (≥25 nmol/L and <50 nmol/L), insufficiency group (≥50 nmol/L and <75 nmol/L) and sufficiency group (≥75 nmol/L). Histopathological classification was confirmed by intraoperative findings. Results The serum level of 25(OH)D was significantly lower in patient group [23.99(20.55,29.54)nmol/L] than that of control group [42.94(35.68,51.04) nmol/L] (P<0.01), and which was also significantly lower in four seasons than that of controls (P<0.05). The serum levels of 25(OH)D were significantly higher in summer group than those of winter group in both patient and control groups (P<0.008 3). The proportion of patients with serious deficiency of 25(OH)D was significantly higher in spring and winter groups in patient group, which was significantly lower in summer group (P<0.01). There was no significant difference in patients with serious deficiency of 25(OH)D between four seasons (P<0.01). For control group, there was a higher proportion of cases with deficiency of 25(OH)D in four seasons, and there was no significant difference in the distribution of seasons (P>0.05). In patient group, there were 107 cases of caseous necrosis type, 56 cases of hyperplasia type, and the proportion of caseous necrosis type was significantly higher in the severe deficiency group (79.17%, 76/96) than that of deficiency group (46.27%, 31/67, P<0.01). Conclusion Excluding the effect of season, vitamin D deficiency is associated with susceptibility to spinal tuberculosis and histopathologic classification.

Objective To study the ages at natural menopause of the women in Jilin Province, and to illustrate its influencing factors among the women in Jilin Province.Methods Through multistage stratified cluster random sampling method,23 050 people aged from 18 to 79 years were drew from nine states(a total of 32 areas)of Jilin province.The data of these residents were collected with the questionnaire and physical examinations by face-to-face interview.The number of selected female sample was 11 098. Finally, 4 881 postmenopausal women were selected.Complex weighted computation was used to estimate the ages at natural menopause.One-way ANOVA was used to compare the ages at natural menopause of the women with different birth years. Multiple linear regression analysis were used to examine the influencing factors of the ages at natural menopause. Results The mean and median ages at natural menopause were (49.11±4.19)years and 50.00 years,respectively.There were 4 881 cases of postmenopausal women,among them the women with age at natural menopause<40 years,40 year≤age at natural menopause≤45 years,46 years≤ age at natural menopause≤53 years,age at natural menopause≥54 years and age at natural menopause missing accounted for 2.27%(111 cases),13.17%(643 cases),71.97%(3 513 cases),11.74% (573 cases),and 0.85%(41 cases),respectively.Converted to birth years by age,70-79 years old was 1933-1942 birth years,60-69 years old was 1943-1952 birth years and 57-59 years old was 1953-1955 birth years.The age at natural menopause in Jilin province was statistically significant among the women with different birth years(F=21.178,P<0.001).By SNK-q test among three different birth year groups, the age at natural menopause was different between any two groups among three different birth year groups and the ages at natural menopause of 1953-1955 birth year group,1943-1952 birth year group and 1943-1952 birth year group were 50.38 years,49.51 years and 48.81 years.The age at natural menopause in urban of Jilin province was statistically significant among the women with different birth years(F=16.633,P<0.001).By SNK-q test among three different birth year groups,the age at natural menopause was different between any two groups among three different birth year groups and the ages at natural menopause of 1953-1955 birth year group,1943-1952 birth year group and 1943-1952 birth year group were 50.77 years,49.73 years,and 48.85 years,respectively.The age at natural menopause in rural of Jilin province was statistically significant among the women with different birth years(F=7.400,P=0.001 ). By SNK-q test among three different birth year groups, the age at natural menopause was different between 1953-1955 birth year group and the other two groups and the ages at natural menopause of 1953-1955 birth year group,1943-1952 birth year group and 1943-1952 birth year group were 50.09 years,49.33 years,and 48.74 years,respectively.The multiple linear regression results indicated that BMI and exercise were positively correlated with the age at natural menopause,but smoking and mental health evaluation were negatively.Consumption frequency of vegetables,fruits,bean products,and meat was no correlated with the age at natural menopause.Conclusion The differences of the ages at natural menopause between the women with different birth years are statistically significant in Jilin Province;BMI, smoking, exercise,and mental health are the influencing factors of the age at natural menopause.

Objective To analyze the mutations of causal genes in 5 children with primary distal renal tubular acidosis (dRTA),and explore their association of genotype and phenotype,so as to raise the awareness of the disease.Methods The whole exome sequencing was used to identify mutations in these 5 children from 5 families.Results A total of 4 different mutations of ATP6V0A4 gene were found in 2 dRTA children,including a novel heterozygous intron mutation (c.639 + 1G＞ A),a reported heterozygous nonsense variant (c.580C ＞T,p.Arg194*) and 2 novel heterozygous duplications (c.1504dupT,p.Tyr502Leufs*22;c.2351dupT,p.Phe785Ilefs*28).Two novel heterozygous missense mutations of ATP6V 1B 1 gene (c.409C ＞ T,p.Pro 137Ser;c.904C ＞ T,p.Arg302Trp) were identified in the third child,and a heterozygous missense mutation of SLC4A1 gene (c.1765C ＞ A,p.Arg589Ser) previously reported was found in the fourth child.No mutation of the dRTA-related causal genes was found in the fifth child.Furthermore,the mutations of causal genes in each of the first three children were compound heterozygous,which were consistent with the autosomal recessive inheritance pattern,and the variant from the fourth child was de novo.Conclusions The present study has found 7 mutations,including 5 novel variants,which enriches the human gene mutation database (HGMD) and contributes to a better understanding of the disease mechanisms.

Objective To analyze and identify the mutations in SGLT2 gene of nine Chinese families with FRG, and determine the renal threshold for glucose excretion (RTG), so as to explore the association of genotype and RTG. Methods All coding regions of SGLT2 gene, including intron exon boundaries, were analyzed using PCR followed by direct sequence analysis. Quantitative test for 24?hour urine glucose and RTG were measured among 9 probands (21 patients) and their family members from 9 pedigrees (total 25 subjects). The differences in renal glucose thresholds between patients with different genotypes (heterozygotes and compound heterozygotes; c.886(-10_-31) del heterozygotes and other heterozygotes) were compared. Results Twelve mutations were identified by SGLT2 gene analysis, including 10 novel ones that were not included in HGMD:c.331T>C, p.W111R;c.374T>C, p.M125T; c.394C>T, p.R132C; c.612G>C, p.Q204H; c.829C>T, p.P277S; c.880G>A, p.D294N;c.1129G>A, p.G377S; c.1194C>A, p.F398L; c.1540C>T, p.P514S; c.1573C>T, p.H525Y. In thisstudy, the mutation c.886(-10_-31)del that is specific to Chinese population accounted for about 28％of the total alleles (5/18). The RTG values of patients with compound heterozygous mutations were much lower than those with simple heterozygous mutations [(1.28 ±0.10) vs (5.14±0.77) mmol/L; P<0.001];and c.886(-10_-31)del heterozygotes had significant lower RTG values than others [(4.43 ± 0.37) vs (5.70 ± 0.51) mmol/L, P<0.001]. Conclusions Ten novel mutations which may be related to FRG are found in this study, and c.886(-10-31)del may be a hot?spot mutation in Chinese patients. Compound heterozygotes had much lower RTG values than simple heterozygotes.

Objective:To evaluate the availability and safety of laparoscopic pyeloplasty with extracorporeal ureteral tailor.Methods:Clinical data of 26 patients with ureteropelvic junction obstruction (UPJO)who were treated by laparoscopic combined with extracorporeal ureteral tailor pyeloplasty in our hospital from March 2016 to August 2019 were retrospectively analyzed. There were 19 males and 7 females. 22 cases had unilateral lesion, including 6 cases on the right side and 16 cases on the left; 2 cases were bilateral. The average age was 22.3 years old (6-54 years). 19 cases felt discomfort in the renal region and 7 cases were asymptomatic. The mean body mass index was 21.7 kg/m 2 (17.2- 26.4 kg/m 2). 5 cases had mild hydronephrosis, 17 cases had moderate hydronephrosis and 4 cases had severe hydronephrosis. 6 cases combined with cross vessels. In all the 26 cases, the ureter was pulled out of the abdomen through a laparoscopic incision, cut lengthways in vitro, sutured at the lowest point, and then returned it to the abdomen. Then, double J tube implantation and ureteropelvic anastomosis were performed under the laparoscopy. Results:26 cases were completed successfully without conversion, with the average operation time of 99 minutes (50-158 minutes), the average blood loss of 19.4 ml (10-50 ml), the average hospital stay of 6.5 days (5-11 days), and the average drainage indwelling time of 5.3 days (4-10 days). For complications, urine leakage occurred on the 3rd day after the operation in 1 case, and the daily drainage fluid was more than 500 ml, which decreased suddenly after 4 days. Postoperative average follow-up was 10.8 months (6-24 months). Renal region pain disappeared in all patients. CT reexamination 3 months after the operation showed that hydronephrosis was alleviated or disappeared in 24 cases, and there was no significant change in 2 cases compared with the preoperative images, but no progress was found in the subsequent reexamination, so we didn't deal with the hydronephrosis again.Conclusions:Laparoscopic pyeloplasty combined with extracorporeal ureteral tailor is minimally invasive and flexible, which greatly reduces the difficulty and time of operation, and has a high success rate.

Objective To compare the etiological constitution of recurrent miscarriage (RM) between patients with consecutive two and three or more miscarriages through combining the routine examination results and embryonic karyotype. Methods Patients with a history of two or more consecutive clinical miscarriages(≤12 weeks of gestation)consulting in the RM clinic of the First Affiliated Hospital of Sun Yat-sen University from March 2011 to January 2016 were collected. Six hundred and ninety-six with detailed history recorded, routine clinical examinations of RM and at least once embryonic karyotype were ultimately enrolled in this study. Their etiological constitution of RM were analyzed in groups of consecutive two and three or more miscarriage. The etiologies of RM in analysis consisted of women age, body mass index (BMI), chromosome abnormalities of couples, uterine abnormalities, endocrinology abnormalities and antiphospholipid syndrome(APS). Results (1)Among 696 patients, the abnormal embryonic karyotypes was 60.6%(422/696)and routine RM etiologies was 32.2%(224/696), leaving the ratio of unexplained RM was only 29.0%(202/696).(2)A total of 717 embryo karyotype were found in 696 patients, included 21 cases with twice embryo karyotype results the percentage of normal embryo was 39.7%(285/717), while abnormal ones was 60.3%(432/717). Among the types of abnormal karyotype, the most common ones (>10%)were trisomy 16(19.2%, 83/432), monosome X(11.3%, 49/432)and trisomy 22(10.9%, 47/432). (3)Among the 696 RM patients, the number of two and three or more miscarriages were respectively 446(64.1%,446/696)and 250(35.9%,250/696). Comparing groups of three or more miscarriages with two miscarriages, there were significant differencein older age as well as uterine adhesion(P<0.05). But no difference was found in body mass index(BMI), the rates of chromosome abnormalities of couples, uterine abnormalities except uterine adhesion, endocrinology abnormalities and APS (all P>0.05) between two groups. Conclusions The abnormal embryonic karyotype is the most common cause of first-trimester RM. The etiological constitution of two and three or more recurrent miscarriages is accordant, suggesting that routine clinical examination and the embryonic karyotype should be started following two consecutive clinical early miscarriages.

Objective To analyze the mutations of SLC12A1 gene in nine Chinese families with Bartter syndrome type I (BS1),and analyze the relationship between genotype and phenotype.Methods The next generation sequencing was used to detect mutations in nine BS1 patients including eight with antenatal BS (aBS) and one with classical BS (cBS).Clinical characteristics and biochemical findings at the first admission as well as follow-up were reviewed.Results 15 different mutations of SLC12A1 gene were identified,including 11 novel ones.Among nine probands,seven were compound heterozygotes,two were homozygotes.All patients presented with polydipsia and polyuria,and eight with growth retardation.All patients had lower than-normal serum chloride concentration,metabolic alkalosis,and elevated basal renin activity and aldosterone,and seven had hypokalemia.Through treatment of indomethacin and/or potassium chloride,biochemical indicators could roughly restored normal.Conclusion These findings will enrich the human gene mutation database (HGMD) and provide valuable references to the genetic counseling and diagnosis for Chinese population.

The gene mutations of a patient with fructose-1,6-bisphosphatase (FBPase) deficiency and her parents were analyzed and her clinical manifestations, laboratory tests, and genetic characteristics were reviewed. The molecular analysis of FBP1 gene showed a G residue duplication at base 960 in exon 7(c. 960dupG) in this patient while her parents carried the heterozygous c. 960dupG mutation. The prominent clinical feature of this patient was the benign course of the disease with age. However, acute attack could be triggered by stress, long-time fasting, a large amounts of fructose intake, etc. The typical clinical manifestations were severe lactic acidosis, hypoglycemia, and elevated liver enzymes.